Rheumatoid arthritis: pathogenesis and therapeutic advances

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes of disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control inflammation and decrease bone destruction, the overall remission rates of RA still stay at a low level. Therefore, uncovering the pathogenesis of RA and expediting clinical transformation are imminently in need. Here, we summarize the immunological basis, inflammatory pathways, genetic and epigenetic alterations, and metabolic disorders in RA, with highlights on the abnormality of immune cells atlas, epigenetics, and immunometabolism. Besides an overview of first‐line medications including conventional DMARDs, biologics, and small molecule agents, we discuss in depth promising targeted therapies under clinical or preclinical trials, especially epigenetic and metabolic regulators. Additionally, prospects on precision medicine based on synovial biopsy or RNA‐sequencing and cell therapies of mesenchymal stem cells or chimeric antigen receptor T‐cell are also looked forward. The advancements of pathogenesis and innovations of therapies in RA accelerates the progress of RA treatments.

Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact

“…As previously noted in this review, various interleukins participate in the pathogenesis of RA, such as TNF-α, IL-1β, and IL-6, among others [ 28 ], as RA is a disease in which many of its comorbidities are associated with metabolic problems or muscle wasting, which contribute to functional disability and a worse disease prognosis [ 33 , 34 , 35 ]. Therefore, several authors have been interested in studying molecules that simultaneously affect all these factors.…”

“…On the other hand, synovial macrophages release various cytokines that participate in the symptoms of RA pathology, mainly interleukin (IL)-1, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, which enhance inflammation through the nuclear factor kappa (NF-k) β pathway [ 27 , 28 ], although IL-12, IL-15, IL-18, IL-17, IL-23, and transforming growth factor-beta (TGF-β) also participate in the physiopathogenesis [ 29 ]. Together, all of these molecules and mechanisms cause a pro-inflammatory environment in patients with RA, reflected not only as persistent inflammation in peripheral joints, such as in the hands, feet, and wrists, but also in ways that cause the patient to present with systemic inflammation that can affect various tissues and organs [ 30 ].…”